study to test the safety and tolerability of pf-07220060 in participants with advance solid tumors

Conditions: Liposarcoma; Prostate Cancer; Breast Neoplasms; Adenocarcinoma of Lung

Summary: this is a phase 1/2a, open label, multicenter, nonrandomized, multiple dose, safety, tolerability, pharmacokinetic and pharmacodynamic study of pf-07220060 administered as a single agent and then in combination with endocrine therapy. the study consists of two parts and a china and japan monotherapy cohort. part 1 includes dose escalation cohorts evaluating pf-07220060 as single agent or in combination with endocrine therapy or enzalutamide, as well as a food effect cohort and a ddi cohort part 2 includes dose expansion cohorts evaluating pf-07220060 in combination with endocrine therapy or enzalutamide. in part 1a, single escalating doses of pf-07220060 alone will be administered to determine the maximum tolerated dose (mtd) and select the recommended dose for expansion in part 1b and part 1c, pf-07220060 will be administered in combination with 1 of 2 endocrine therapies (letrozole and fulvestrant, respectively). in part 1d, food effect assessment of pf-07220060 at the rp2d dose level from the part 1a will be conducted in part 1e, the effect of pf-07220060 on the pk of midazolam will be evaluated (ddi) in part 1f, escalating dosed of pf-07220060 will be administered in combination with enzalutamide part 1b and part 1c may commence at mtd or before reaching the mtd at a dose level in part 1a. part 2a is a dose expansion cohort with fulvestrant and will explore more than one dose of pf-07220060 in participants diagnosed with mbc. part 2b and part 2c are expansion for combination therapy of pf-07220060 with letrozole and fulvestrant, respectively. part 2d is the expansion cohort for combination therapy of pf-07220060 with enzalutamide. part 2e is an expansion cohort to evaluate pf-07220060 monotherapy versus pf-07220060 plus fulvestrant combination therapy. the china monotherapy cohort will evaluate safety, tolerability and pk of pf-07220060 administered as single agent in chinese participants. the japan monotherapy cohort will evaluate safety, tolerability and pk of pf-07220060 administered as a single agent in japanese participants.


Eligibility criteria:
inclusion criteria * part 1: breast cancer (bc) * refractory hormone receptor positive (hr+), human epidermal growth factor receptor 2 negative (her2-) bc * part 1a/part 1d/part1e also include: refractory hr-positive/her2-positive bc * part 1: tumors other than bc (part 1a/part 1d/part 1e): nsclc, prostate, crc, liposarcoma, or tumors with previously confirmed cdk4 or ccnd1 amplification according to local standard tests * part 1f: prostate cancer * part 2a, 2b, 2c and 2e: * hr-positive/her2-negative bc * patients who are either postmenopausal women or pre/peri-menopausal (part 2c only) * part 1d: metastatic castration resistant prostate cancer * lesion: * part 1: evaluable lesion (including skin or bone lesion only) * part 2a, 2b, 2c and 2e: measurable lesion per recist v1.1 * part 2d: participants with evaluable disease as per pcwg3; participants with bone metastases only are allowed. participants with biochemical recurrence only are excluded. * prior systemic treatment * part 1: hr-positive/her2-negative bc * at least 1 line of soc, including cd4/6 inhibitor therapy for advanced or metastatic disease, or if cdk4/6 inhibitors are not considered appropriate in the opinion of the investigator * at least 1 line of anti-endocrine in countries without cdk4/6 inhibitor approval or reimbursement, for advanced or metastatic disease * hr-positive/her2-positive bc (parts 1a/1d/1e): at least 1 prior treatment of approved her2 targeting therapy * tumors other than bc (parts 1a/1d/1e/1f): tumor that is resistant to at least 2 lines of soc for advanced or recurrent disease or for which no standard therapy is available * part 2a and 2e: participants must have received at least 1 line of standard of care (including prior cdk4/6i) for advanced/metastatic disease; prior chemo is allowed; prior fulvestrant, mtor and/or pi3k inhibitors are allowed * part 2b: participants who have not received any prior systemic anti-cancer therapies for advanced/metastatic bc * part 2c: * progressed during treatment or within 12 months of completion of adjuvant therapy with an aromatase inhibitor if postmenopausal, or tamoxifen if pre or perimenopausal, or * progressed while on or within 1 month after the endo the prior aromatase inhibitor therapy for advanced/metastatic bc if postmenopausal or prior endocrine treatment for advanced/metastatic bc if pre or perimenopausal * one previous line of chemotherapy for advanced/metastatic disease is allowed in addition to endocrine therapy * part 2d: * received prior abiraterone; enzalutamide and cdk4i naive * 0-1 line of chemotherapy is allowed general inclusion criteria * all participants must be refractory to or intolerant of existing therapies known to provide clinical benefit for their condition. * eastern cooperative oncology group (ecog) performance status (ps) 0 or 1 * adequate renal, liver, and bone marrow function exclusion criteria: * part 1d: participants who have had a gastrectomy or have dietary or other restrictions that preclude a 10 hour overnight fast or consumption of the high fat, high calorie meal * part 2b: prior neoadjuvant or adjuvant treatment with a non-steroidal aromatase inhibitor with disease recurrence while on or within 12 months of completing treatment. prior treatment with any cdk4/6 inhibitor * part 2c: prior treatment with any cdk inhibitor, fulvestrant, everolimus, or any agent whose mechanism of action is to inhibit the pi3k-mtor pathway * known active uncontrolled or symptomatic central nervous system (cns) metastases carcinomatous meningitis, or leptomeningeal disease * other active malignancy within 3 years prior to randomization, except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ * major surgery or radiation within 4 weeks prior to study intervention * last anti-cancer treatment within 2 weeks prior to study intervention * participation in other studies involving investigational drug(s) within 4 weeks prior to study entry * pregnant or breastfeeding female participant * active inflammatory gastrointestinal (gi) disease, known diverticular disease or previous gastric resection or lap band surgery including impairment of gastrointestinal function or gi disease

Keywords: cdk4 inhibitor breast cancer enzalutamide fulvestrant letrozole endocrine therapy colorectal cancer (crc) solid tumors